Bioreactors, also referred to as fermenters, are a part of biotechnological apparatuses. They have a closed reaction chamber, in which eukaryotic or prokaryotic cells are cultivated under conditions that are as optimal, defined and controlled as possible. Conversions of substances, mostly automated and controlled by process engineering, are researched, optimised and performed using the boundary conditions necessary for the organism and in the presence of the primary and secondary substances required for the process.
In typical biotechnological methods carried out on “benchtop scale” (laboratory scale), glass reactor vessels are frequently used. This allows an autoclavable bioreactor to be designed in which the glass reactor vessel can be steam sterilised in one piece in an autoclave. It is then necessary in such cases to separate the connections for the entire reactor vessel from the control units before autoclaving. Connections are typically in the form of hose connectors such as clamp screw connections, push-in connectors, crimp connections or the like. Such an autoclavable design of the bioreactor thus requires that functional components of the biotechnological apparatus which connect to the bioreactor itself are mounted on the reactor vessel as efficiently as possible and can be dismantled again when autoclaving is due.
Another bioreactor design takes the form of single-use bioreactors, in which the reactor vessel, for example, is used in one cultivation process only, whereas functional elements assigned to the reactor vessel, such as stirrer drives, or the temperature control unit for exhaust gas removal and/or cultivation chamber, can be reused. In this connection also, it is necessary that functional components of the biotechnological apparatus which are coupled to the bioreactor be mounted on the reactor vessel and dismantled again after use as efficiently as possible.
Bioreactors are usually operated in a temperature range of about 10° C. to about 50° C., due to the characteristics of the biological cultures used therein, and also, in rather rare cases of extremophile cultures, at temperatures between −20 and 150° C. Various methods and devices have been proposed for controlling the temperature of cultures. One method involves directly heating the exterior of the reactor vessel with the aid of thermally coupled electrical heating elements, using heating blankets or temperature-control jaws containing integrated elements, for example. Cooling is effected using immersed heat exchangers, such as cooling fingers or cooling coils through which a coolant flows.
In connection with the aforementioned heating, the exterior of the reactor vessel can be cooled, alternatively, by means of a thermally coupled device, typically of a jaw-like or pot-like design, the temperature of which can be lowered by a coolant passed through it with a controllable volumetric flow rate.
One known alternative is to use double-walled reactor vessels, with a pre-heated or pre-cooled fluid flowing through the outer compartment separated from the interior of the reactor vessel. The fluid is typically heated in a cycle with integrated heating, for example by means of an electrical heater. The fluid is cooled by means of a secondary coolant in the heat exchanger or by replacement, i.e. by mixing additional coolant to the cycle and simultaneously removing the same amount of warm fluid.
Another known alternative, finally, is to use indirect external heating in the form of radiant heat, for example an infrared source. Cooling is then performed in a manner as described above.
A control loop for controlling the temperature of the cultivation chamber in the bioreactor is typically formed by a temperature sensor, appropriately immersed into the culture in the cultivation chamber, and a temperature controller. In rare cases, the supply temperature is also controlled.
For small, parallel cultures, several miniaturised reactor vessels, such as multi-well plates or shake flasks, are arranged in temperature-controlled compartments, for example incubators or thermal chambers. In these cases, only the temperature of the gas, for example a mixture of N2, O2 and CO2, is suitably controlled in the compartment, typically. The temperature of the culture is not measured directly or by feedback, typically, which can lead to undefined temperatures within the culture, particularly in the case of cultures with a high cell density and strong specific biological heat production.
In research and development, autoclavable bioreactor systems that are not fixedly installed are frequently used. In such systems, the reactor or culture vessel is temporarily separated, for sterilisation purposes, from those system components that cannot be steam sterilised. This involves additional handling in the case of known methods and devices for controlling temperature. It is necessary to cut the fluid circulation, which means that appropriate coupling and shut-off devices must be provided. Depending on the fluid used for temperature control, the latter must also be removed from the subsystem to be sterilised. Another disadvantage of fluid-operated cooling devices in many cases is the strong formation of condensate (from ambient air) on system components, for example on connection tubes or the like. Analogous disadvantages ensue from connecting and disconnecting temperature-control elements in single-use bioreactors.
Since the heat capacity of the (mostly aqueous) temperature-control fluid is relatively high, it cannot be conditioned (cooled) in the short term when this is necessary, but must typically be kept permanently available in suitable form. In addition to the frequently very poor energy efficiency of the devices used for this purpose, such as recirculating coolers and/or poorly insulated conduits, this often causes an additional nuisance in the form of noise and heat in the workplace.
In most cases, the electrical heater is operated with primary grid voltage. One disadvantage of this is that electrical safety must be ensured by means of appropriate insulation, which involves additional expense in the case of autoclavable bioreactors that are not fixedly installed. There is also the economic disadvantage that suitable heating elements with different operating voltages must be provided for every market that is targeted.
Another specific disadvantage of all the known systems is their poor energy efficiency, particularly in cooling mode.
Regarding control systems, EP 1 533 893 A2 discloses a generator control system. In the case where a user changes a set state of apparatuses, an apparatus operation control portion repressively controls the apparatuses, in spite of an instruction of a control signal according to that change, so that an increasing amount of power consumption of the apparatuses obtained from an apparatus power consumption measuring portion will not exceed an increasing amount of the generating capacity of a generator obtained from a generating capacity measuring portion so as to gradually bring it closer to a target set state set up by the user. However, further improvements are sought.